Vitamin B<sub>12</sub>-Folate Interrelationships

Shane, Barry; Stokstad, E. L. R.

doi:10.1146/annurev.nu.05.070185.000555

Cited by 284 publications

(141 citation statements)

References 37 publications

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“…Following hydrolysis of AdoHcy, the resulting homocysteine can undergo remethylation to methionine or be irreversibly catabolized by the transsulfuration pathway. Folate-dependent remethylation occurs with the donation of a methyl group by 5-methyltetrahydrofolate (5-CH 3 -THF) through the action of B 12 -dependent methionine synthase (MS) (8). In hepatic tissue, betaine derived from the oxidation of choline can also serve as a folate-independent source of methyl groups for homocysteine remethylation via the enzyme betaine-homocysteine S-methyltransferase (BHMT).…”

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confidence: 99%

Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid

Nieman

Rowling

Garrow

et al. 2004

Journal of Biological Chemistry

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The hepatic enzyme glycine N-methyltransferase (GNMT) plays a major role in the control of methyl group and homocysteine metabolism. Because disruption of these vital pathways is associated with numerous pathologies, understanding GNMT control is important for evaluating methyl group regulation. Recently, gluconeogenic conditions have been shown to modulate homocysteine metabolism and treatment with glucocorticoids and/or all-trans-retinoic acid (RA)-induced active GNMT protein, thereby leading to methyl group loss. This study was conducted to determine the effect of diabetes, alone and in combination with RA, on GNMT regulation. Diabetes and RA increased GNMT activity 87 and 148%, respectively. Moreover, the induction of GNMT activity by diabetes and RA was reflected in its abundance. Cell culture studies demonstrated that pretreatment with insulin prevented GNMT induction by both RA and dexamethasone. There was a significant decline in homocysteine concentrations in diabetic rats, owing in part to a 38% increase in the abundance of the transsulfuration enzyme cystathionine ␤-synthase; treatment of diabetic rats with RA prevented cystathionine ␤-synthase induction. A diabetic state also increased the activity of the folate-independent homocysteine remethylation enzyme betaine-homocysteine S-methyltransferase, whereas the activity of the folatedependent enzyme methionine synthase was diminished 52%. In contrast, RA treatment attenuated the streptozotocin-mediated increase in betaine-homocysteine Smethyltransferase, whereas methionine synthase activity remained diminished. These results indicate that both a diabetic condition and RA treatment have marked effects on the metabolism of methyl groups and homocysteine, a finding that may have significant implications for diabetics and their potential sensitivity to retinoids.

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mentioning

confidence: 99%

Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid

Nieman

Rowling

Garrow

et al. 2004

Journal of Biological Chemistry

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“…The pathogenesis of hyperhomocysteinemia in hypothyroidism has not been fully understood, but a reduction in renal function and methylene tetrahydrofolate reductase activity, an enzyme involved in the catalysis of Hcy and its remethylation to methionine, have been claimed as possible responsible factors [38, 39]. In the present study, mean serum creatinine concentration was comparable between the subjects with SCF and NCF patterns but methylene tetrahydrofolate reductase activity was not investigated.…”

Section: Discussionmentioning

confidence: 59%

Interaction of Plasma Homocysteine and Thyroid Hormone Concentrations in the Pathogenesis of the Slow Coronary Flow Phenomenon

Evrengül

Tanrıverdi

Enli³

et al. 2006

Cardiology

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Background and Objective: The slow coronary flow (SCF) phenomenon is an angiographic observation and a well-recognized clinical entity characterized by delayed opacification of vessels in a normal coronary angiogram due to reasons yet unclear. Thyroid hormones exert significant effects on plasma homocysteine (Hcy) levels and microvascular resistance. Recently, several investigators have consistently reported that elevation of the plasma Hcy level can severely disturb vascular endothelial function and play a role in the pathogenesis of SCF. Accordingly, we investigated the levels of plasma Hcy and thyroid hormones and their relationship in patients with SCF. Method: Forty-four patients with angiographically proven SCF (Group I) (mean age 55.5 ± 10.4 years, 26 males) and 44 cases with normal coronary flow (NCF) pattern (Group II) (mean age 53.9 ± 11 years, 22 males) with similar risk profiles were enrolled in the study. Coronary flow patterns of the cases were determined by the thrombolysis in myocardial infarction (TIMI) frame count method. The coronary TIMI frame counts were calculated separately for each coronary artery and their average was determined as the mean TIMI frame count for each subject. Serum levels of free tri-iodothyronine (fT₃), free thyroxine (fT₄), thyroid stimulating hormone (TSH) and Hcy were measured. Patients with thyroid disease or on medications with a potential to affect thyroid functions were excluded. Results: There were no statistically significant differences between the groups concerning the demographic characteristics and major cardiovascular risk factors. Mean TIMI frame counts of SCF and NCF groups were 45.9 ± 12 and 23.3 ± 3.7, respectively. fT₄ (ng/dl) and TSH (µIU/ml) levels of the two groups were similar (p > 0.05). The level of fT₃, the active metabolite of the thyroid hormone family, was dramatically reduced in the SCF group when compared to the NCF group (2.3 ± 0.2 vs. 3.0 ± 0.3, p = 0.0001, respectively). Plasma Hcy levels of patients with SCF were found to be significantly higher than controls (12.2 ± 4.9 vs. 8.5 ± 2.9, p = 0.0001, respectively). Correlation analysis showed a significant negative correlation between the plasma fT₃and Hcy levels and the mean TIMI frame counts (r = –0.31, p = 0.003 vs. r = –0.66, p = 0.0001). Moreover, there was a significant positive correlation between the plasma Hcy levels and the mean TIMI frame counts (r = 0.58, p = 0.0001). Also, fT₃ was the only significant determinant of the variance of Hcy in multiple regression analysis (r = –0.30, p = 0.005). Conclusion: fT₃ levels were decreased and plasma Hcy levels were increased significantly in patients with SCF as compared to controls. This finding suggests that thyroid hormones and/or (?) a possible disturbance in their metabolism may be responsible for the elevated levels of plasma Hcy in patients with SCF and may play a role in the pathogenesis of the SCF phenomenon.

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“…MTR is an enzyme that converts homocysteine to methionine by using folate as a methyl group carrier [5]. Although its presence in the placenta has been reported [8], the localization is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…MTR mediates the process of methionine synthesis from homocysteine using folate as a methyl group carrier [5]. MTHFR generates the main circulatory form of folate, 5-methyltetrahydrofolate, from 5,10-methylenetetrahydrofolate [6,7].…”

Section: Introductionmentioning

confidence: 99%

Localization of Folate Metabolic Enzymes, Methionine Synthase and 5,10-Methylenetetrahydrofolate Reductase in Human Placenta

Shin¹,

Kim²,

Park

et al. 2014

Gynecol Obstet Invest

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Background: Normal fetal development requires adequate folate levels during pregnancy. Although folate metabolic enzymes have important roles in the maintenance of normal fetal development, the location of folate metabolic enzymes, methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR), has not been previously examined. Methods: We investigated the expression of MTR and MTHFR in human term placenta obtained from normal and pregnancy-induced hypertension (PIH) patients. Results: MTR is expressed in the villous syncytiotrophoblast and MTHFR is expressed in the extravillous trophoblast. There was no difference in the quantity and location of these enzymes between control and PIH patients. Conclusion: These results suggest that MTR in the villous trophoblast participates in the metabolism of homocysteine by using folate, and MTHFR in the extravillous trophoblast is associated with extratrophoblast invasion.

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Vitamin B₁₂-Folate Interrelationships

Cited by 284 publications

References 37 publications

Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid

Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid

Interaction of Plasma Homocysteine and Thyroid Hormone Concentrations in the Pathogenesis of the Slow Coronary Flow Phenomenon

Localization of Folate Metabolic Enzymes, Methionine Synthase and 5,10-Methylenetetrahydrofolate Reductase in Human Placenta

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Vitamin B12-Folate Interrelationships

Cited by 284 publications

References 37 publications

Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid

Modulation of Methyl Group Metabolism by Streptozotocin-induced Diabetes and All-trans-retinoic Acid

Interaction of Plasma Homocysteine and Thyroid Hormone Concentrations in the Pathogenesis of the Slow Coronary Flow Phenomenon

Localization of Folate Metabolic Enzymes, Methionine Synthase and 5,10-Methylenetetrahydrofolate Reductase in Human Placenta

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Vitamin B₁₂-Folate Interrelationships